DESCRIPTION: (modified from applicant's abstract) The long-term objective is to develop a non-viral, liposomal gene delivery system appropriate for systemic delivery in vivo. This proposed delivery system does not use cationic lipids (the most common class of liposome formulations for gene delivery in use today) but instead uses a formulation strategy similar to long-circulating, sterically-stabilized liposomes currently in use for intravenous drug delivery. The principal hypothesis is that a sterically-stabilized gene delivery system will exhibit one or more of the following advantages over current gene delivery formulations: 1) Prolonged circulation times, leading to a more uniform organ and tissue distribution of gene expression, 2) increased ability to extravasate from vascular beds, leading to enhanced gene expression in cell types other than endothelium, monocytes, and macrophages, 3) preferential accumulation at sites of tumors within organs and tissues, 4) a reduction of inflammatory and other cytotoxic effects currently observed with cationic lipid formulations, and most importantly, 5) gene expression without the necessity for cell division. The proposal has three specific aims to be achieved during the two-year "Pilot and Feasibility Study": 1) A sterically-stabilized liposome formulation will be modified and tested for effective in vivo delivery using and adult mouse model. 2) Gene expression, pharmokinetics, and biodistribution will be assessed for prolonged circulation times. 3) Organ tissues will be examined histologically to assess gene expression in cell types outside the vasculature.